1785: Withering recommends fox-glove for asthma

William Withering (1741-1799)

William Withering was a contemporary of William Cullen.  While Cullen was the first to describe asthma as spasmotic constriction of the muscular fibers of the bronchi, Withering was the first to recommend for asthma a remedy called foxglove.

Withering was a physician from Shrophire, England. He graduated from Edinburgh in 1766 and then had a "large and lucrative practice at Birmingham.  

While he had other accomplishments, he is best known for his discovery of a treatment called foxglove for asthma caused by dropsy of the heart.  

So, what is dropsy of the heart? Or, better yet, what is dropsy? 

Dropsy is essentially an old term referring to edema, or swelling and redness.  It comes from the Greek term hudrop-piasis hudrops, which refers to a dropsical person.  The term hudro means hydro, which means water.  (3)

Since there was no standardization in those days, sometimes other terms were used to mean the same thing. For instance, the terms "congestion" and "hydrops" and "anascara" were also used when referring to the build-up of fluid in a certain part of the body.

When physicians like Withering observed the build-up of fluid in a certain part of the body, or a certain organ, he would simply use dropsy, hydrops or congestion, followed by the part of the body or organ affected.  To understand how these terms were used consider the following chart. 

Old term	Description	New term
Cerebral Dropsy	Fluid on the brain	Hydrocephalis
Dropsy of ankles, legs, feet	Fluid in ankles, legs feet	Pedal edema
Dropsy of the lungs Congestion of lungs	Fluid in lungs	Pulmonary edema
Dropsy of the throat	Swollen throat	Croup or Epiglotitis
Hydrops Abdominus	Fluid in the abdominal cavity	Ascites
Hydrops Pectoris	Fluid in cavity surrounding the lungs	Pleural Effusion

Of course it must be understood for our purposes that dropsy of the lungs was usually associated with asthma, which was a generic term meaning dyspnea, or shortness of breath.  

So, what is foxglove?

Foxglove was a common remedy used in Withering's day and age for just about any ailment in the book. However, it was not prescribed because it had any beneficial effect, but because it worked to extricate fluid from the body, and thereby balance the humors.  

Foxglove the flower

You see, the dogmatic ideas of Hippocrates were still taught in medical schools, although they were adjusted slightly to suit the times.  

Noting the abuse of this medicine (sort of like albuterol in the 21st century), Withering set out to learn more about this remedy, where it came from, and what it was actually good for.  

Through his research, he learned that foxglove was first discovered by Fuchsius in 1542. He gave it the name foxglove because the blossom of the plant looked like the finger of a glove. (5, page xiv)

Shortly thereafter, he said in describing its discovery, the experimenting began, with various parts of the plant being ingested or added into the recipes of various foods and drinks and ingested that way. The toxic effects of the plant were soon noted, such that taken in large amounts caused vomiting. (5, page xiv)

Another effect soon observed was that foxglove also acted as a diuretic, meaning that it made you pee. Upon further experiment, it was learned that it worked great as a remedy for various diseases. Of course since anatomical wisdom was anemic in those days, the reason it worked, and for what remedies it truly benefited, remained inextricable. (1)(5, page 2)

Eventually the remedy was discovered to be useful for asthma, although, once again, the reason for this remained a mystery.  Therefore it was suspected that it its diuretic and nauseating properties probably helped to balance the humors, thus curing asthma.  

Knowledge that foxglove helped in cases of asthma passed to a lady who kept this a secret for many years. When she was an elderly lady living in Shrophire, Withering heard wind of her remedy for asthma, and interviewed her to learn more about it. She said foxglove was good for dropsy, and that it caused nausea (1)(5, page 2)

So now Withering started his own experiments with the remedy. He verified that in high doses it did cause nausea, although he soon learned that even patients given small amounts of the remedy had increased urination. (5, page 4)

He then realized that it was the diuretic effect of the plant, and not the nauseating effect, that was beneficial for asthma. It was by this means he learned that it was useful for dropsy. In fact, he noted that "if the medicine purges, it is almost certain to fail in its desired effect." (5, page 4)

It was in this way that he discovered the desired effect of the medicine was removal of excessive fluid in the body, which helped with pretty much any ailment that resulted in dropsy, hydropsy or congestion. (5, page 2-6)

In other words, he learned foxglove was a "powerful diuretic." It was useful as a remedy for dropsy of the lungs and hydrops of the legs, ankles and feet.  It was also useful for hydrops abdominis and hydrops pectoris.  (5, page 2-6)

It was not, however, effective for cerebral dropsy caused by head trauma. (1)

In 1785, about ten years after he began his research on foxglove, he published his findings in the book "Account of the Foxglove." He described foxglove and all the remedies he discovered it benefited.  (5, page v) 

However, as any judicious physician describing a new treatment should do, he warned that physicians should restrain themselves in its use, although not condemn and reject it as "dangerous and unmanageable." (5, page v) 

The book, he said, was essentially...

...a protest against the abuses of digitalis, which were already creeping in. (1)

Regarding foxglove and asthma, Withering wrote the following in his book:

ASTHMA

(9) THE true spasmodic asthma, a rare disease is not relieved by Digitalis. 

(10) In the greater part of what are called asthmatical cases, the real disease is anasarca of the lungs, and is generally to be cured by diuretics. This is almost always combined with some swelling of the legs

(11) There is another kind of asthma, in which change of posture does not much affect the patient. I believe it to be caused by an infarction-of the lungs. It is incurable by diuretics; but it is often accompanied with a degree of anasarca, and so far it admits of relief. 

ASTHMA and ANASARCA

(12) IF the asthma be of the kind mentioned at (9 & 11) diuretics can only remove the accompanying anasarca. But if the affection of the breath depends also, upon cellular effusion, as it mostly does, the patient may be taught to expect a recovery.

ASTHMA and ASCITES

(13) A RARE combination, but not incurable if the the abdominal viscera are sound. The asthma is here most probably of the anasarcous kind (10) and this being seldom confined to the lungs only, the disease generally appears,in the following form.

ASTHMA, ASCITES, and ANASARCA.

(14) THE curability of this combination will depend upon the circumstances mentioned in the "'preceding section, taking also into the account the strength or weakness of the patient. (5, page 196-7)

He also recommended asthma for phthisis pulmonalis, although he said this was not a new discovery as other physicians had found it useful and had recommended it. (5, page 9)

Note that Withering, as with other physicians of his era, regarded asthma in it's pure form, which would be asthma accompanied by no other ailments, as being a rare condition.  He offered no new wisdom about pure asthma.

He said most patients who present with asthma (dyspnea) present with more than just "pure asthma," and in these cases, the most common complication is anascara of the lungs, and it is this that he proved benefited from foxglove for its diuretic effect.

He must have also observed that many of these patients also present with dropsy of the ankles.

Thanks to his research, the medicine foxglove (digitalis) was entered into the Edinburgh Pharmacopoeia in 1783, but did not appear in the London Pharmacopoeia until 1809.(1)

Note: During the course of the next 50 years, it would be discovered that asthma caused by dropsy of the lungs or hydrops pulmonais, were actually caused by heart or kidney failure. These would ultimately become disease entities of their own, and therefore would be separated from the umbrella term asthma. In 1827 Richard Bright became the first person to distinguish between dropsy of the lungs caused by heart failure and kidney failure.  .

References: 

1. Garrison, "An introduction to the history of medicine," 1921, 3rd edition, Philadelphia and London, W.B. Saunders Company , page 367-368, 408)
2. Cullen, William, "First Lines of the Practice of the Phsych," 1784, Edinburgh, Vol. 3, 4th ed., 387-88, 397
3. "Dropsy," The Free Dictionary by Farlex, http://www.thefreedictionary.com/dropsy, accessed 6/23/13
4. "Digitalis," Drugs.com, http://www.drugs.com/npp/digitalis.html, accessed 6/23/13
5. Withering, William, "An account of the foxglove and some of its medical uses with practical remarks on dropsy and other diseases," 1785, London, Paternoster Row

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